Objective To investigate the role of Astragali and Angelica (A&A) of Chinese herbs in acute renal ischemia/reperfusion injury, and the related intracellular signal transduction mechanism. Methods Acute ischemic renal injury in rats was induced by clamping in renal pedicel for 45 minutes. Rats in therapy group were given a single dose (2 ml/day) of A&A for 3 days before clamping, and then continued for another 3 days. Forty-five minutes after clamping and at different reperfusion time, serum creatinine (Scr) and renal pathological changes were taken and compared in both groups. The proliferating cell nuclear antigen (PCNA) positive cells were detected by immunohistochemistry. Extracelluar regulating kinase (ERK) and c-Jun N-terminal kinase (JNK) activity was assayed by specific substrate phosphorylation with immunoprecipitation. Results At the 24th hour of reperfusion, Scr was lower in A&A group than that in the control. Much less necrotic tubular cells， casts， and more PCNA-positive cells were found in A&A group. ERK activity decreased after clamping, and recovered at 5 minutes of reperfusion. There was no difference between the two groups. JNK activity did not change after ischemia, but increased at 5 minutes and peaked at 20 minutes of reperfusion. JNK activity was significantly higher in A&A group than that in the control group. Conclusion A&A protected kidney against ischemic insult and accelerated both functional and histological recovery after acute renal ischemia/reperfusion injury, which may associate with the change of JNK signaling pathway.
Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK, play an important role in transducting environmental stimuli to the transcriptional machinery in the nucleus in mammalian cells by virtue of their ability to phosphorylate and regulate the activity of various transcription factors. It was recently found that the changes in activity of MAPKs occurred during ischemia/reperfusion, but the biological significance of the changes was still controversial.
